Synthesis of (‐)‐Cannabidiol (CBD), (‐)‐Δ9‐ and (‐)‐Δ8‐Tetrahydrocannabinols, Encapsulation of CBD with Nanoparticles for Controlled Delivery and Biological Evaluation

Abstract Cannabidiol (CBD) is garnering increasing interest due to its significant biological activity. This natural compound is one of the major cannabinoids in Cannabis sativa L. In this work, we describe the encapsulation of CBD in solid and hollow pH‐sensitive poly (4‐vinylpyridine) (solid@ p 4VP and hollow@ p 4VP) nanoparticles, and temperature‐sensitive poly ( N ‐isopropylacrylamide) (solid@ p NIPAM and hollow@ p NIPAM) nanoparticles for transport and release CBD in a controlled manner. The CBD loading into these smart polymeric systems was effective and their release profiles, solubility and resistance to stomach and intestinal conditions were evaluated, showing satisfactory properties and improved bioavailability with respect to free CBD. Finally, the A549 human lung cancer cell line was used as lung adenocarcinoma epithelial cellular model to carry out preliminary assays of the in vitro activity of the vehiculized CBD. For all these studies, synthetic CBD was employed, for which a new efficient and scalable synthesis of cannabinoids has been developed.